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洛哌丁胺以剂量依赖的方式增加小鼠肠道转运时间,且对不同肠道微生物类群的影响具有治疗持续时间依赖性。

Loperamide increases mouse gut transit time in a dose-dependent manner with treatment duration-dependent effects on distinct gut microbial taxa.

作者信息

Hjørne Anna Pii, Mortensen Martin Steen, Licht Tine Rask, Laursen Martin Frederik

机构信息

National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.

出版信息

Gut Microbiome (Camb). 2025 May 2;6:e7. doi: 10.1017/gmb.2025.5. eCollection 2025.

DOI:10.1017/gmb.2025.5
PMID:40336798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056420/
Abstract

Intestinal transit time has been recognized as an important factor in shaping the gut microbiota, although causality remains to be firmly demonstrated. The aim of this study was to evaluate the effect of different loperamide doses on the mouse intestinal transit time and to investigate the effects of increasing transit time on the gut microbial community. Loperamide significantly increased the transit time in a dose-dependent manner. Additionally, we observed a significant difference between the control group and the loperamide-treated groups in the abundance of the bacterial families , and after 7 days of loperamide treatment, with the bacterial families responding to the increased transit time at different rates. Fermentation of faeces obtained from the same mice, with or without loperamide, demonstrated that the observed effects on gut microbiota were not a result of direct interactions between loperamide and the gut microbiota but rather a consequence of loperamide-induced increased intestinal transit time. In the cecum of the mice, we found higher levels of propionate in the high-dose group compared to the control and low-dose groups. Collectively, our findings establish that an altered transit time is causal to changes in the composition and activity of the microbiome.

摘要

肠道转运时间已被认为是塑造肠道微生物群的一个重要因素,尽管因果关系仍有待确凿证明。本研究的目的是评估不同剂量洛哌丁胺对小鼠肠道转运时间的影响,并研究转运时间延长对肠道微生物群落的影响。洛哌丁胺以剂量依赖的方式显著延长了转运时间。此外,我们观察到对照组和洛哌丁胺治疗组之间在细菌家族丰度上存在显著差异,并且在洛哌丁胺治疗7天后,不同细菌家族对转运时间延长的反应速率不同。对同一小鼠服用或未服用洛哌丁胺的粪便进行发酵实验表明,观察到的对肠道微生物群的影响不是洛哌丁胺与肠道微生物群直接相互作用的结果,而是洛哌丁胺诱导的肠道转运时间延长的结果。在小鼠盲肠中,我们发现高剂量组的丙酸盐水平高于对照组和低剂量组。总的来说,我们的研究结果表明,转运时间的改变是微生物组组成和活性变化的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/533ef6f14d13/S2632289725000052_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/bb96393d5728/S2632289725000052_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/c4842d2360b5/S2632289725000052_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/5f31e8e1c401/S2632289725000052_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/39835fdd52f5/S2632289725000052_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/533ef6f14d13/S2632289725000052_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/bb96393d5728/S2632289725000052_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/c4842d2360b5/S2632289725000052_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/5f31e8e1c401/S2632289725000052_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/39835fdd52f5/S2632289725000052_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4442/12056420/533ef6f14d13/S2632289725000052_fig5.jpg

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Nat Microbiol. 2024 Dec;9(12):3210-3225. doi: 10.1038/s41564-024-01856-x. Epub 2024 Nov 27.
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Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.膳食纤维通过肠道微生物群的代谢相互作用来指导微生物色氨酸代谢。
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CFP/Yit: An Inbred Mouse Strain with Slow Gastrointestinal Transit.
CFP/Yit:一种胃肠道转运缓慢的近交系小鼠。
Dig Dis Sci. 2024 Jun;69(6):2026-2043. doi: 10.1007/s10620-024-08420-x. Epub 2024 Apr 15.
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Gut microbiota response to in vitro transit time variation is mediated by microbial growth rates, nutrient use efficiency and adaptation to in vivo transit time.肠道微生物群对体外传输时间变化的反应是由微生物生长速度、营养利用效率和对体内传输时间的适应介导的。
Microbiome. 2023 Nov 6;11(1):240. doi: 10.1186/s40168-023-01691-y.
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L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice.L通过调节小鼠肠道微生物群的组成来缓解洛哌丁胺引起的便秘。
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